Endothelial signals modulate hepatocyte apicobasal polarization in zebrafish.
Emerging evidence indicates that paracrine signals from endothelial cells play a role in tissue differentiation and organ formation [1-3]. Here, we identify a novel role for endothelial cells in modulating hepatocyte polarization during liver organogenesis. We find that in zebrafish, the apical domain of the hepatocytes predicts the location of the intrahepatic biliary network. The refinement of hepatocyte polarization coincides with the invasion of endothelial cells into the liver, and these endothelial cells migrate along the maturing basal surface of the hepatocytes. Using genetic, pharmacological, and transplantation experiments, we provide evidence that endothelial cells influence the polarization of the adjacent hepatocytes. This influence of endothelial cells on hepatocytes is mediated at least in part by the cell-surface protein Heart of glass and contributes to the establishment of coordinately aligned hepatocyte apical membranes and evenly spaced intrahepatic conduits.
Sakaguchi
Takuya F
TF
Department of Biochemistry and Biophysics, Program in Developmental Biology, University of California, San Francisco, California 94158, USA. takuya.sakaguchi@ucsf.edu
Sadler
Kirsten C
KC
Crosnier
Cecile
C
Stainier
Didier Y R
DY
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D016764:Cell Polarity; D042783:Endothelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000196:embryology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D038081:Organogenesis; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000378:metabolism
D020410:Activated-Leukocyte Cell Adhesion Molecule; D008562:Membrane Glycoproteins; D029961:Zebrafish Proteins; C482644:heg1 protein, zebrafish